The objectives of research proposed in this request are continuations of those pursued in this laboratory over the past several years. (1) To study the enzymatic and biochemical constitution of human bloods in health and as modified by disease. (2) To define aberrations induced by acquired disease, by inherited enzyme deficiency states, and by such factors as nutritional status and medications. (3) To adopt and expand methodology applicable to metabolic studies of blood cells (4) To exploit genetically determined molecular lesions in terms of obtaining more insight into normal metabolism, its regulation and modulation. (5) to determine the mode of genetic transmission of such heritable abnormalities. Established technology in the laboratory currently permits assay of all glycolytic enzymes and intermediates, enzymes of the hexosemonophosphate shunt, and certain enzymes of glutathione and nucleotide metabolism.